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Synaptic Density and Neuronal Metabolic Function Measured by Positron Emission Tomography in the Unilateral 6-OHDA Rat Model of Parkinson's Disease.

ABSTRACT: Parkinson's disease (PD) is caused by progressive neurodegeneration and characterised by motor dysfunction. Neurodegeneration of dopaminergic neurons also causes aberrations within the cortico-striato-thalamo-cortical (CSTC) circuit, which has been hypothesised to lead to non-motor symptoms such as depression. Individuals with PD have both lower synaptic density and changes in neuronal metabolic function in the basal ganglia, as measured using [¹¹C]UCB-J and [¹⁸F]FDG positron emission tomography (PET), respectively. However, the two radioligands have not been directly compared in the same PD subject or in neurodegeneration animal models. Here, we investigate [¹¹C]UCB-J binding and [¹⁸F]FDG uptake in the CSTC circuit following a unilateral dopaminergic lesion in rats and compare it to sham lesioned rats. Rats received either a unilateral injection of 6-hydroxydopamine (6-OHDA) or saline in the medial forebrain bundle and rostral substantia nigra (n = 4/group). After 3 weeks, all rats underwent two PET scans using [¹⁸F]FDG, followed by [¹¹C]UCB-J on a separate day. [¹⁸F]FDG uptake and [¹¹C]UCB-J binding were both lower in the ipsilateral striatal regions compared to the contralateral regions. Using [¹¹C]UCB-J, we could detect an 8.7% decrease in the ipsilateral ventral midbrain, compared to a 2.9% decrease in ventral midbrain using [¹⁸F]FDG. Differential changes between hemispheres for [¹¹C]UCB-J and [¹⁸F]FDG outcomes were also evident in the CSTC circuit's cortical regions, especially in the orbitofrontal cortex and medial prefrontal cortex where higher synaptic density yet lower neuronal metabolic function was observed, following lesioning. In conclusion, [¹¹C]UCB-J and [¹⁸F]FDG PET can detect divergent changes following a dopaminergic lesion in rats, especially in cortical regions that are not directly affected by the neurotoxin. These results suggest that combined [¹¹C]UCB-J and [¹⁸F]FDG scans could yield a better picture of the heterogeneous cerebral changes in neurodegenerative disorders.

SUBMITTER: Raval NR

PROVIDER: S-EPMC8636601 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Positron emission tomography (PET) visualizes increased cellular [F]fluorodeoxyglucose ([F]FDG) uptake. Pulmonary hypertension (PH) is conceived of a proliferative disease of the lung vessels. Increased glucose uptake can be quantified as pulmonary [F]FDG uptake via PET imaging. Because the angioproliferative mechanisms in PH are still in need of further description, the aim of the present study was to investigate whether [F]FDG PET/CT imaging can elucidate these pathophysiologic mechanisms in different etiologies of PH.Patients (n?=?109) with end-stage pulmonary disease being evaluated for lung transplant were included in this observational study. Mean standardized uptake value (SUVmean) of predefined regions of interest in lung parenchyma (LP), left (LV), and right ventricle (RV) of the heart, and SUVmax in pulmonary artery (PA) were determined and normalized to liver uptake. These SUV ratios (SUVRs) were compared with results from right heart catheterization (mean pulmonary artery pressure [mPAP], pulmonary vascular resistance [PVR]), and serum N-terminal pro-brain natriuretic peptide. Group comparisons were performed and Pearson correlation coefficients (r) were calculated.The [F]FDG uptake ratios in LP, RV, RV/LV, and PA, but not in LV, were found to be significantly higher in both patients with mPAP ?25?mm Hg (P?=?0.013, P?=?0.006, P?=?0.049, P?=?0.002, P?=?0.68, respectively) and with PVR ?480?dyn·s/cm (P?<?0.001, P?=?0.045, P?<?0.001, P?<?0.001, P?=?0.26, respectively). The [F]FDG uptake in these regions positively correlated also with mPAP, PVR, and N-terminal pro-brain natriuretic peptide. The SUVR of PA positively correlated with the SUVR of LP and RV (r?=?0.55, r?=?0.42, respectively).Pulmonary and cardiac [F]FDG uptake in PET imaging positively correlated with the presence and severity of PH in patients with end-stage pulmonary disease. Increased glucose metabolism in the central PAs seems to play a certain role in terms of severity of PH. These results suggest that [F]FDG-PET imaging can help understand the pathophysiology of PH as a proliferative pulmonary disease.

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Synaptic Density and Neuronal Metabolic Function Measured by Positron Emission Tomography in the Unilateral 6-OHDA Rat Model of Parkinson's Disease.

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